@article{RN6179,
   author = {Beekman, R. and Valkhof, M. G. and Sanders, M. A. and van Strien, P. M. and Haanstra, J. R. and Broeders, L. and Geertsma-Kleinekoort, W. M. and Veerman, A. J. and Valk, P. J. and Verhaak, R. G. and Löwenberg, B. and Touw, I. P.},
   title = {Sequential gain of mutations in severe congenital neutropenia progressing to acute myeloid leukemia},
   journal = {Blood},
   volume = {119},
   number = {22},
   pages = {5071-7},
   note = {1528-0020
Beekman, Renée
Valkhof, Marijke G
Sanders, Mathijs A
van Strien, Paulette M H
Haanstra, Jurgen R
Broeders, Lianne
Geertsma-Kleinekoort, Wendy M
Veerman, Anjo J P
Valk, Peter J M
Verhaak, Roel G
Löwenberg, Bob
Touw, Ivo P
Case Reports
Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't
United States
2012/03/01
Blood. 2012 May 31;119(22):5071-7. doi: 10.1182/blood-2012-01-406116. Epub 2012 Feb 27.},
   abstract = {Severe congenital neutropenia (SCN) is a BM failure syndrome with a high risk of progression to acute myeloid leukemia (AML). The underlying genetic changes involved in SCN evolution to AML are largely unknown. We obtained serial hematopoietic samples from an SCN patient who developed AML 17 years after the initiation of G-CSF treatment. Next- generation sequencing was performed to identify mutations during disease progression. In the AML phase, we found 12 acquired nonsynonymous mutations. Three of these, in CSF3R, LLGL2, and ZC3H18, co-occurred in a subpopulation of progenitor cells already in the early SCN phase. This population expanded over time, whereas clones harboring only CSF3R mutations disappeared from the BM. The other 9 mutations were only apparent in the AML cells and affected known AML-associated genes (RUNX1 and ASXL1) and chromatin remodelers (SUZ12 and EP300). In addition, a novel CSF3R mutation that conferred autonomous proliferation to myeloid progenitors was found. We conclude that progression from SCN to AML is a multistep process, with distinct mutations arising early during the SCN phase and others later in AML development. The sequential gain of 2 CSF3R mutations implicates abnormal G-CSF signaling as a driver of leukemic transformation in this case of SCN.},
   keywords = {Adult
Bone Marrow/metabolism
Cell Transformation, Neoplastic/*genetics/metabolism
Granulocyte Colony-Stimulating Factor/therapeutic use
Humans
Leukemia, Myeloid, Acute/complications/drug therapy/*genetics/metabolism
Male
*Mutation
Neoplasm Proteins/*genetics/metabolism
Neutropenia/complications/congenital/drug therapy/*genetics/metabolism
Stem Cells/metabolism},
   ISSN = {0006-4971},
   DOI = {10.1182/blood-2012-01-406116},
   year = {2012},
   type = {Journal Article}
}

{"_id":"ekxBM9STW5zkFhCz8","bibbaseid":"beekman-valkhof-sanders-vanstrien-haanstra-broeders-geertsmakleinekoort-veerman-etal-sequentialgainofmutationsinseverecongenitalneutropeniaprogressingtoacutemyeloidleukemia-2012","author_short":["Beekman, R.","Valkhof, M. G.","Sanders, M. A.","van Strien, P. M.","Haanstra, J. R.","Broeders, L.","Geertsma-Kleinekoort, W. M.","Veerman, A. J.","Valk, P. J.","Verhaak, R. G.","Löwenberg, B.","Touw, I. P."],"bibdata":{"bibtype":"article","type":"Journal Article","author":[{"propositions":[],"lastnames":["Beekman"],"firstnames":["R."],"suffixes":[]},{"propositions":[],"lastnames":["Valkhof"],"firstnames":["M.","G."],"suffixes":[]},{"propositions":[],"lastnames":["Sanders"],"firstnames":["M.","A."],"suffixes":[]},{"propositions":["van"],"lastnames":["Strien"],"firstnames":["P.","M."],"suffixes":[]},{"propositions":[],"lastnames":["Haanstra"],"firstnames":["J.","R."],"suffixes":[]},{"propositions":[],"lastnames":["Broeders"],"firstnames":["L."],"suffixes":[]},{"propositions":[],"lastnames":["Geertsma-Kleinekoort"],"firstnames":["W.","M."],"suffixes":[]},{"propositions":[],"lastnames":["Veerman"],"firstnames":["A.","J."],"suffixes":[]},{"propositions":[],"lastnames":["Valk"],"firstnames":["P.","J."],"suffixes":[]},{"propositions":[],"lastnames":["Verhaak"],"firstnames":["R.","G."],"suffixes":[]},{"propositions":[],"lastnames":["Löwenberg"],"firstnames":["B."],"suffixes":[]},{"propositions":[],"lastnames":["Touw"],"firstnames":["I.","P."],"suffixes":[]}],"title":"Sequential gain of mutations in severe congenital neutropenia progressing to acute myeloid leukemia","journal":"Blood","volume":"119","number":"22","pages":"5071-7","note":"1528-0020 Beekman, Renée Valkhof, Marijke G Sanders, Mathijs A van Strien, Paulette M H Haanstra, Jurgen R Broeders, Lianne Geertsma-Kleinekoort, Wendy M Veerman, Anjo J P Valk, Peter J M Verhaak, Roel G Löwenberg, Bob Touw, Ivo P Case Reports Clinical Trial Journal Article Research Support, Non-U.S. Gov't United States 2012/03/01 Blood. 2012 May 31;119(22):5071-7. doi: 10.1182/blood-2012-01-406116. Epub 2012 Feb 27.","abstract":"Severe congenital neutropenia (SCN) is a BM failure syndrome with a high risk of progression to acute myeloid leukemia (AML). The underlying genetic changes involved in SCN evolution to AML are largely unknown. We obtained serial hematopoietic samples from an SCN patient who developed AML 17 years after the initiation of G-CSF treatment. Next- generation sequencing was performed to identify mutations during disease progression. In the AML phase, we found 12 acquired nonsynonymous mutations. Three of these, in CSF3R, LLGL2, and ZC3H18, co-occurred in a subpopulation of progenitor cells already in the early SCN phase. This population expanded over time, whereas clones harboring only CSF3R mutations disappeared from the BM. The other 9 mutations were only apparent in the AML cells and affected known AML-associated genes (RUNX1 and ASXL1) and chromatin remodelers (SUZ12 and EP300). In addition, a novel CSF3R mutation that conferred autonomous proliferation to myeloid progenitors was found. We conclude that progression from SCN to AML is a multistep process, with distinct mutations arising early during the SCN phase and others later in AML development. The sequential gain of 2 CSF3R mutations implicates abnormal G-CSF signaling as a driver of leukemic transformation in this case of SCN.","keywords":"Adult Bone Marrow/metabolism Cell Transformation, Neoplastic/*genetics/metabolism Granulocyte Colony-Stimulating Factor/therapeutic use Humans Leukemia, Myeloid, Acute/complications/drug therapy/*genetics/metabolism Male *Mutation Neoplasm Proteins/*genetics/metabolism Neutropenia/complications/congenital/drug therapy/*genetics/metabolism Stem Cells/metabolism","issn":"0006-4971","doi":"10.1182/blood-2012-01-406116","year":"2012","bibtex":"@article{RN6179,\n author = {Beekman, R. and Valkhof, M. G. and Sanders, M. A. and van Strien, P. M. and Haanstra, J. R. and Broeders, L. and Geertsma-Kleinekoort, W. M. and Veerman, A. J. and Valk, P. J. and Verhaak, R. G. and Löwenberg, B. and Touw, I. P.},\n title = {Sequential gain of mutations in severe congenital neutropenia progressing to acute myeloid leukemia},\n journal = {Blood},\n volume = {119},\n number = {22},\n pages = {5071-7},\n note = {1528-0020\nBeekman, Renée\nValkhof, Marijke G\nSanders, Mathijs A\nvan Strien, Paulette M H\nHaanstra, Jurgen R\nBroeders, Lianne\nGeertsma-Kleinekoort, Wendy M\nVeerman, Anjo J P\nValk, Peter J M\nVerhaak, Roel G\nLöwenberg, Bob\nTouw, Ivo P\nCase Reports\nClinical Trial\nJournal Article\nResearch Support, Non-U.S. Gov't\nUnited States\n2012/03/01\nBlood. 2012 May 31;119(22):5071-7. doi: 10.1182/blood-2012-01-406116. Epub 2012 Feb 27.},\n abstract = {Severe congenital neutropenia (SCN) is a BM failure syndrome with a high risk of progression to acute myeloid leukemia (AML). The underlying genetic changes involved in SCN evolution to AML are largely unknown. We obtained serial hematopoietic samples from an SCN patient who developed AML 17 years after the initiation of G-CSF treatment. Next- generation sequencing was performed to identify mutations during disease progression. In the AML phase, we found 12 acquired nonsynonymous mutations. Three of these, in CSF3R, LLGL2, and ZC3H18, co-occurred in a subpopulation of progenitor cells already in the early SCN phase. This population expanded over time, whereas clones harboring only CSF3R mutations disappeared from the BM. The other 9 mutations were only apparent in the AML cells and affected known AML-associated genes (RUNX1 and ASXL1) and chromatin remodelers (SUZ12 and EP300). In addition, a novel CSF3R mutation that conferred autonomous proliferation to myeloid progenitors was found. We conclude that progression from SCN to AML is a multistep process, with distinct mutations arising early during the SCN phase and others later in AML development. The sequential gain of 2 CSF3R mutations implicates abnormal G-CSF signaling as a driver of leukemic transformation in this case of SCN.},\n keywords = {Adult\nBone Marrow/metabolism\nCell Transformation, Neoplastic/*genetics/metabolism\nGranulocyte Colony-Stimulating Factor/therapeutic use\nHumans\nLeukemia, Myeloid, Acute/complications/drug therapy/*genetics/metabolism\nMale\n*Mutation\nNeoplasm Proteins/*genetics/metabolism\nNeutropenia/complications/congenital/drug therapy/*genetics/metabolism\nStem Cells/metabolism},\n ISSN = {0006-4971},\n DOI = {10.1182/blood-2012-01-406116},\n year = {2012},\n type = {Journal Article}\n}\n\n","author_short":["Beekman, R.","Valkhof, M. G.","Sanders, M. A.","van Strien, P. M.","Haanstra, J. R.","Broeders, L.","Geertsma-Kleinekoort, W. M.","Veerman, A. J.","Valk, P. J.","Verhaak, R. G.","Löwenberg, B.","Touw, I. P."],"key":"RN6179","id":"RN6179","bibbaseid":"beekman-valkhof-sanders-vanstrien-haanstra-broeders-geertsmakleinekoort-veerman-etal-sequentialgainofmutationsinseverecongenitalneutropeniaprogressingtoacutemyeloidleukemia-2012","role":"author","urls":{},"keyword":["Adult Bone Marrow/metabolism Cell Transformation","Neoplastic/*genetics/metabolism Granulocyte Colony-Stimulating Factor/therapeutic use Humans Leukemia","Myeloid","Acute/complications/drug therapy/*genetics/metabolism Male *Mutation Neoplasm Proteins/*genetics/metabolism Neutropenia/complications/congenital/drug therapy/*genetics/metabolism Stem Cells/metabolism"],"metadata":{"authorlinks":{}}},"bibtype":"article","biburl":"https://verhaaklab.com/files/verhaak.bib","dataSources":["iFXeF2qjAL2y5TeTz"],"keywords":["adult bone marrow/metabolism cell transformation","neoplastic/*genetics/metabolism granulocyte colony-stimulating factor/therapeutic use humans leukemia","myeloid","acute/complications/drug therapy/*genetics/metabolism male *mutation neoplasm proteins/*genetics/metabolism neutropenia/complications/congenital/drug therapy/*genetics/metabolism stem cells/metabolism"],"search_terms":["sequential","gain","mutations","severe","congenital","neutropenia","progressing","acute","myeloid","leukemia","beekman","valkhof","sanders","van strien","haanstra","broeders","geertsma-kleinekoort","veerman","valk","verhaak","löwenberg","touw"],"title":"Sequential gain of mutations in severe congenital neutropenia progressing to acute myeloid leukemia","year":2012}